Merck Research Labs, West Point, PA 19486, USA.
Neuroimage. 2014 Jan 1;84:724-32. doi: 10.1016/j.neuroimage.2013.09.036. Epub 2013 Sep 21.
fMRI can objectively measure pain-related neural activities in humans and animals, providing a valuable tool for studying the mechanisms of nociception and for developing new analgesics. However, due to its extreme sensitivity to subject motion, pain fMRI studies are performed in animals that are immobilized, typically with anesthesia. Since anesthesia could confound the nociceptive processes, it is unknown how well nociceptive-related neural activities measured by fMRI in anesthetized animals correlate with nociceptive behaviors in conscious animals. The threshold to vocalization (VT) in response to an increasing noxious electrical stimulus (NES) was implemented in conscious rats as a behavioral measure of nociception. The antinociceptive effect of systemic (intravenous infusion) lidocaine on NES-induced fMRI signals in anesthetized rats was compared with the corresponding VT in conscious rats. Lidocaine infusion increased VT and suppressed the NES-induced fMRI signals in most activated brain regions. The temporal characteristics of the nociception signal by fMRI and by VT in response to lidocaine infusion were highly correlated with each other, and with the pharmacokinetics (PK) of lidocaine. These results indicate that the fMRI activations in these regions may be used as biomarkers of acute nociception in anesthetized rats. Interestingly, systemic lidocaine had no effect on NES-induced fMRI activations in the primary somatosensory cortex (S1), a result that warrants further investigation.
功能性磁共振成像 (fMRI) 可客观地测量人类和动物的疼痛相关神经活动，为研究伤害感受机制和开发新的镇痛药物提供了有价值的工具。然而，由于其对受试者运动极其敏感，疼痛 fMRI 研究在被固定的动物中进行，通常使用麻醉。由于麻醉可能会混淆伤害感受过程，因此尚不清楚在麻醉动物中通过 fMRI 测量的伤害感受相关神经活动与清醒动物的伤害感受行为之间的相关性如何。通过递增的有害电刺激（NES）引起的发声阈值（VT）在清醒大鼠中作为伤害感受的行为测量来实现。比较了全身（静脉输注）利多卡因对麻醉大鼠 NES 诱导的 fMRI 信号的镇痛作用与清醒大鼠的相应 VT。利多卡因输注增加了 VT，并抑制了大多数激活的脑区中的 NES 诱导的 fMRI 信号。通过 fMRI 和 VT 对利多卡因输注的伤害感受信号的时间特征彼此高度相关，并且与利多卡因的药代动力学（PK）相关。这些结果表明，这些区域的 fMRI 激活可作为麻醉大鼠急性伤害感受的生物标志物。有趣的是，全身利多卡因对初级体感皮层（S1）中 NES 诱导的 fMRI 激活没有影响，这一结果值得进一步研究。
